莫达非尼觉醒作用机制研究进展  

Mechanism profile for arousal effects of modafinil

作　　者：陈长瑞[1] 曲卫敏[1,2] 黄志力[1,3,2] 

机构地区：[1]复旦大学上海医学院药理学系 [2]复旦大学脑科学研究院,上海200032 [3]复旦大学医学神经生物学国家重点实验室

出　　处：《中国临床药理学与治疗学》2010年第12期1428-1434,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金："重大新药创制"科技重大专项(2009ZX09303-006);国家自然科学基金(30625021;30821002;30970955;30901797;31070957);上海市科学技术委员会基金(09PJ1401800;09JC1402500;10XD1400400;10441901600);上海市重点学科建设项目(B119);教育部博士点基金(20070246186)

摘　　要：莫达非尼是强效促觉醒药物,主要用于治疗发作性睡病等原因引起的白天嗜睡。莫达非尼和多巴胺(dopamine,DA)转运体有一定亲和性,可增加脑内DA释放,也影响去甲肾上腺素(no-radrenaline,NA)、5-羟色胺(serotonin,5-HT)、谷氨酸、γ-氨基丁酸(-γaminobutyric acid,GA-BA)、orexin和组胺能等神经系统,但觉醒作用机制存有众多争议。行为学研究发现,DA转运体基因敲除(knock-out,KO)动物给予莫达非尼后,不能产生显著的觉醒作用;D2受体KO)动物对莫达非尼的觉醒作用显著降低,前处理D1受体拮抗剂,莫达非尼对D2受体KO小鼠的促觉醒作用消失,提示多巴胺能D1/D2受体在莫达非尼促觉醒作用中至关重要,其他神经递质的变化可能是觉醒的继发性作用。本文综述莫达非尼觉醒作用机制研究进展。Modafinil is a potent wake-promoting compound with low abuse potential used in the treatment of narcolepsy and day time sleepiness.The compound is reported to affect multiple neurotransmitter systems such as catecholamines,serotonin,glutamate,GABA,orexin,and histamine,however,the molecular mechanism by which modafinil increases wakefulness is debated.It was previously testified that arousal effects of modafinil were not exhibited in dopamine transporter KO mice;furthermore,treatment of dopamine（DA） D2 receptor（D2R）-deficient mice with D1R-specific antagonists completely abolished arousal effects of modafinil.These findings strongly indicate that dopamine and dopaminergic D1R and D2R are essential for the wakefulness caused by modafinil,and its influence on other neurotransmitter systems may result from enhanced dopaminergic activity and wakefulness.This review summarizes the progress on mechanism profile for arousal effects of modafinil.

关 键 词：莫达非尼 觉醒 多巴胺 D1受体 D2受体 DA转运体 

分 类 号：R749[医药卫生—神经病学与精神病学]